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Article Excerpt
Abstract: Wegener granulomatosis (WG) is a systemic disease of unknown etiology characterized by necrotizing granulomatous inflammation, tissue necrosis, and variable degrees of vasculitis in small and medium-sized blood vessels. The classic clinical pattern is a triad involving the upper airways, lungs and kidneys. Ninety percent of patients present with symptoms involving the upper and/or lower airways, and 80% will eventually develop renal disease. WG should be suspected in any patient with progressive or unresponsive sinus disease, glomerulonephritis, pulmonary hemorrhage, mono-neuritis multiplex or unexplained multisystem disease. Before the routine use of glucocorticoids and cyclophosphamide, the one year mortality was 82%. However in 1973, Fauci and Wolf discovered that daily prednisone and cyclophosphamide induced complete remission in 75% of patients. The continued use of prednisone and cyclophosphamide for 1 year past remission leads to marked improvement in more than 90% of patients; however, is also associated with serious toxicities. Depending on the disease severity, current treatments employ induction with short-term cyclophosphamide followed by less toxic agents such as methotrexate to maintain disease remission. Although it is a rare disorder, it is pertinent to internists because it is a multisystem disease that presents in a variety of ways. We describe a 63-year-old white male with WG who presented with progressively worsening headaches, bilateral eye redness, epistaxis, hemoptysis and an unintentional 20 pound weight loss, and review the current treatment recommendations.
Key Words: Wegener granulomatosis, ANCA, cyclophosphamide, vasculitis, methotrexate
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Wegener granulomatosis (WG) is a multisystemic disease of unknown etiology that classically involves clinical disease of the upper airways, lungs and kidneys. Although it is an uncommon condition, it is relevant to internists because it can present in a variety of ways. We describe a 63-year-old white male with WG who presented with progressively worsening headaches, bilateral eye redness, epistaxis, hemoptysis and a 20 pound unintentional weight loss, and review the current treatment recommendations.
Case Report
A 63-year-old white male with a history of hypertension, diabetes mellitus, hyperlipidemia, and ischemic heart disease was admitted with 2 months of progressively worsening headaches, bilateral eye redness, epistaxis, bloody sputum and a 20 pound unintentional weight loss. The patient, a retired construction worker who hunted and skinned coyotes, was well until 2 months before admission. He developed an intermittent frontal headache which became severe, constant, diffuse and associated with retro-orbital discomfort. These headaches did not worsen with coughing or change in position, nor were they relieved by over-the-counter analgesics (acetaminophen, ibuprofen, etc.). He also developed bilateral eye redness with mild photophobia, nasal congestion, mild epistaxis and the "feeling of fullness" in both ears with decreased hearing. One month before admission, he developed a slightly purulent cough streaked with blood, subjective fevers, night sweats, malaise, easy fatigability and anorexia.
His home medications included aspirin, metoprolol, metformin, Monopril, atorvastatin and Fioricet (acetaminophen + butalbital + caffeine). The patient had a 40-pack year smoking history, although he quit 20 years before the admission. He denied excessive alcohol intake, illicit drug use, and use of herbal medicines. He denied travel or exposure to tuberculosis. There was no history of rhinorrhea, otorrhea, excessive lacrimation, change in visual acuity, chest pain, dyspnea, asthma, allergic rhinitis, abdominal pain, hematuria, arthritis, skin lesions or paresthesias. There was no family history of vasculitis or connective tissue disease.
The patient was a well-developed male who appeared ill. On physical examination, his temperature was 101.3[degrees] Fahrenheit, heart rate was 98 per minute, respirations were 18 per minute, blood pressure was 146/80 mm Hg and oxygen saturation was 98% on room air.
He had bilateral conjunctival injection without retinal exudates, rash or lymphadenopathy. His lung, cardiovascular, abdominal, extremity, musculoskeletal and neurologic examinations were normal except for a 1/6 systolic heart murmur.
His laboratory data at admission included a hemoglobin of 11.2 g/dL (normal range 11.3-15.4 g/dL), white blood cell count of 8,400 per [mm.sup.3] (normal range 3.4-9.2), platelet count of 835,000 per [mm.sup.3] (normal range 142-405 thousand), and an erythrocyte sedimentation rate of 113 mm per hour (normal range 0-15). His albumin level was 2 g/dL (normal range 3.5-5.0 g/dL), aspartate aminotransferase 49 (normal range 5-34 u/L), alanine aminotransferase 82 (normal range 5-55 u/L), C-reactive protein 4.72 mg/dL (normal range 0.0-0.5 mg/dL) and his urinalysis contained 10 to 20 white cells, 10 to 20 red cells and cellular casts. In addition, his proteinuria estimated by spot urine protein and creatinine was 0.5 g/24 hours. The blood levels of urea nitrogen, creatinine, electrolytes, glucose, total bilirubin and thyroid stimulating hormone levels were normal.
A computed tomographic (CT) scan of the head with contrast (not shown) was negative for mass effect, hemorrhage, or brain lesion. Posteroanterior and lateral chest x-rays indicated a new, approximately 3 X 4.5 cm ovoid opacity in the lateral right upper lobe. Enhanced CT scan of the thorax demonstrated bilateral poorly marginated pulmonary parenchymal lesions; the largest being 4 cm and pleural-based in the anterior segment of the right upper lobe (Fig. 1). Purified protein derivative skin test and sputum smears and cultures for acid-fast bacilli were negative. Blood and urine cultures were sterile and urine histoplasma antigen, serum brucella, tularemia, leptospira, coccidioidomycosis and blastomycosis antibody tests were negative. Tests for human immunodeficiency virus, hepatitis A, B and C viruses were also negative. A transesophageal echocardiogram was normal. A bronchoscopic examination showed that the airways were normal and that there were no abnormal secretions. The bronchoalveolar lavage fluid had no malignant cells and was sterile.
[FIGURE 1 OMITTED]
Otorhinolaryngology evaluation identified golden crusty lesions in the nasal cavities with friable mucosa. CT scan of the sinuses showed mucoperiosteal thickening of maxillary, sphenoid and frontal sinuses without paranasal sinus fluid levels (Fig. 2). Ophthalmologic evaluation suggested subacute conjunctivitis only. Tests for antinuclear antibodies and antiglomerular basement membrane antibodies were negative but an antineutrophil cytoplasmic antibody was positive at a titer of 1:160 with a cytoplasmic pattern. Antiproteinase-3 antibody level detected by an antigen-specific enzyme-linked immunoassay was 82.1 U (normal range < 5 U).
[FIGURE 2 OMITTED]
A left nasal septum biopsy was nondiagnostic. Therefore, the patient underwent a wedge resection of the right upper lobe lung lesion. The histopathological examination revealed diffuse thickening of alveolar walls that contained moderate numbers of mononuclear cells and occasional eosinophils. Many of the large- and medium-sized arteries were noted to have mononuclear cells, eosinophils and occasional multinucleated giant cells within their walls, mostly concentrated in the intima. A frequent dense fibrosis and chronic inflammation was noted around these vessels and the adjacent bronchioles. The alveoli contained numerous macrophages, some with hemosiderin, type II pneumocytes and occasional multinucleated giant cells. Small areas of organizing pneumonia and necrosis were noted. Periodic acid-Schiff stain, Giemsa and acid-fast bacilli smear failed to reveal fungi or acid-fast organisms. These histologic findings were consistent with those seen in Wegener granulomatosis (Fig. 3-5).
The patient was treated with intravenous (IV) methylprednisolone 1 g daily for 3 days followed by prednisone 60 mg daily and continuous daily cyclophosphamide 50 mg per day. In addition, he was started on trimethoprim-sulfamethoxazole one double-strength tablet three times weekly for Pneumocystis jiroveci pneumonia prophylaxis and discharged home in stable condition.
Discussion
Wegener granulomatosis (WG) is a systemic disease of unknown etiology characterized by necrotizing granulomatous inflammation and variable degrees of vasculitis in small and medium-sized blood vessels. It was first described by Heinz Klinger in 1931, followed by other investigators, including Rossle in 1933, Friedrich Wegener in 1936 and 1939, and Ringertz in 1947. (1-3) It affects about 3 in 100,000 people, with equal sex distribution. (4) Although known to affect all...
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